Novel products

ABSTRACT

Aliphatic 2,4-diunsaturated amides, substituted with a thiol (mercapto) or hydrocarbon thio group, useful for the control of insects.

Henrick et al.

NOVEL PRODUCTS Inventors: Clive A. Henrick; John B. Siddall,

both of Palo Alto, Calif.

Assignee: Zoecon Corporation, Palo Alto,

Calif.

Filed: Oct. 9, 1973 Appl. No.: 404,632

Related U.S. Application Data Division of Ser. No. 256,605. May 24. 1972, which is a continuation-in-part of Ser. No. 201.189, Nov. 22, 1971, abandoned. which is a continuation-in-part of Ser. No. 191,812, Oct. 22, I971, abandoned.

U.S. Cl 260/402.5, 260/609 R, 260/465.2, 260/399, 260/614 R, 260/601 R [451 Feb. 11, 1975 [5]] Int. Cl. C08h 9/02. C08h 3/00 [58] Field of Search 260/402.5

References Cited UNITED STATES PATENTS 6/1973 Baum 260/399 Primary lituniimW-Elbfit L. Roberts Attorney. Agent. or FirmLee-Louise H. Priest; Donald W. Erickson 6 Claims, No Drawings NOVEL PRODUCTS This is a division of application Ser. No. 256,605,- filed May 24, 1972, which is a continuation-impart of application Ser. No. 201 ,l 89, filed Nov. 22. 1971, now abandoned, which. in turn, is a continuation-in-part of application Ser. No. 191,812, filed Oct. 22, 1971, now abandoned.

This invention relates to novel aliphatic diunsaturated esters and acids, derivatives thereof, intermediates therefor, substituted with thiol (mercapto) or a hydrocarbon thio group, syntheses thereof, and the control of insects. More particularly, the novel unsaturated esters and acids of the present invention are rep resented by the following formula A:

each of m and n is or the positive integer l, 2 or 3: R is hydrogen, lower alkyl, cycloalkyl, aralkyl or aryl; each of R and R is lower alkyl;

each of R R R and R is hydrogen or lower alkyl;

R* is alkyl; and

R is hydrogen, lower alkyl, cycloalkyl, aryl, aralkyl,

lower alkylthiaalkyl, lower alkoxyalkyl, halogen substituted lower alkyl, heterocyclic, lower alkenyl, lower alkynyl or a metal cation, and the acid halides thereof.

The compounds of formula A are useful for the control of insects. The utility of these compounds as insect control agents is believed to be attributablle to their juvenile hormone activity. They are preferably applied to the immature insect, namely during the embryo, larvae or pupae stage in view of their effect on metamorphosis and otherwise cause abnormal development leading to death or inability to reproduce. These compounds are effective control agents for Hemipteran such as Lygaeidae, Miridae and pyrrhocoridae; Lepidopteran such as Pyralidae, Noctuidae and Gelechiidae; Colcapteran such as Tenebrionidae, Crysomelidae and Dermestidae; Dipteran such as mosquitos, flies; Homopteran such as aphids and other insects. The compounds can be applied at low dosage levels of theorder of 0.0] pg. to 25.0 pg. per insect. Suitable carrier substances include liquid or solid carriers, such as water, acetone, xylene, mineral or vegetable oils, talc, vermiculite, natural and synthetic resins and silica. Treatment of insects in accordance with the present invention is accomplished by spraying, dusting or exposing the insects to the vapor of the compounds of formula A. Generally, a concentration of less than ofthe active compound is employed. The formulations can include insect attractants, emulsifying agents or wetting agents to assist in the application and effectiveness of the active ingredient. In the application of the compounds, there is generally employed a mixture of the C-2,3 trans and cis isomers.

In the description hereinafter, each ofm, n, R--R and R -R is as defined hereinabove unless otherwise specified.

In the above formulas, X is bromo or chloro, R is lower alkyl, cycloalkyl, benzyl or phenyl and R is lower alkoxy, cycloalkoxy or arallkoxy.

In the above synthesis, a ketal or acetal of a carbonyl of formula I is converted into a thiol (mercapto) substituted ketal or acetal of the carbonyl of formula 11. Preparation of the thiol can be accomplished for example, using thiourea followed by treatment with base, such as sodium hydroxide or an amine. Suitable methods applicable for preparation of thiols of formula ll from a acetal or ketal of a compound of formula I are described by Cossar et al, J. Org. Chem 27', 93 (1962); Backer, Rec. trav. chim. 54, 215 (1935); Szmuszkovicz, Organic Preparations and Procedures 1 (l 43-45 (1969); and Backer and Dijkstra Rec. trav. chim. 51, 290 (1932). A compound of formula II, or the acetal or ketal thereof, is then alkylated to prepare a thioether of formula III (R is not H). The alkylation can be accomplished using a halide of the hydrocarbon group desired such as lower alkyl iodide. The acetal or ketal protecting group is removed in a conventional manner using dilute acid such as aqueous hydrochloric acid, aqueous sulfuric acid, and the like. A carbonyl of formula III is then reacted with a carbanion of formula IV to prepare the dienoic ester of formula V (R is not bydrogen). Reaction of the carbanion with a carbonyl of formula 11 provides the mercapto compounds of formula V (R is hydrogen). The carbanion is generated from the respective phosphonate with a base such as alkali hydroxide, alkali alkoxide, alkali hydride, and the like. Suitable procedures are described by Pattenden In the second synthesis outlined above of II and III to V1 to V, a carbonyl of formula ll or 111 is reacted with a carbanion of formula IV A using the conditions described above or with an ylid of formula W B to yield an unsaturated ketone of formula VI.

The unsaturated ketone (V1) is then reacted with a carbanion of formula NC to yield a compound of formula V or by Wittig reaction using the ylid (lVD).

(IVC) (IVD) Conversion of V1 into V using carbanion (IVC) can be done using the same conditions as for conversion of 111 into V. Wittig reactions are generally done at higher temperatures such as from room temperature to reflux. The cylids are prepared from the corresponding phosphonium bromide or chloride by treatment with a base substance such as an alkali metal hydride, alkali metal hydroxide or alkali metal carbonate in an organic solvent, such as toluene, benzene, or tetrahydrofuran, or water or aqueous organic solvent depending upon the particular base. The Wittig reagents can be prepared as described in U.S. Pat. No. 3,193,565.

The esters of formula V are converted into the corresponding acid by hydrolysis with base such as potassium carbonate, sodium carbonate, sodium hydroxide, and the like in organic solvent such as methanol or ethanol. Other esters of the present invention can be prepared by transesterification or conversion of the acid into the acid halide by treatment with thionyl chloride, oxalyl chloride, phosphorous pentabromide or the like, and then reacting the acid halide with the alcohol corresponding to the ester moiety desired.

In .another embodiment of the present invention, there is provided thio-acids and thiol esters of formula Vll. Thio-acids and thiol esters can be prepared from the respective acid halide using hydrogen sulfide to prepare the thio-acid and a thiol R" SH or a mercaptide to prepare the thiol ester. Thiol esters can be prepared by alkylation of the sodium salt of a thio-acid of the present invention also. See U.S. Pat. Nos. 3,567,747 and 3,505,366.

l SR

wherein R is hydrogen, lower alkyl, cycloalkyl, aryl or aralkyl.

In another embodiment of the present invention, there is provided ketones and aldehydes of formula VIII. The ketones can be prepared by treatment of an ester (V) or an acid thereof with the appropriate organo-lithium, the organo group corresponding to the ketone moiety desired. The reaction is generally carried out in an organic solvent such as an ether solvent. In addition, acid halides, particularly the acid chloride, can be used for the preparation of ketones of formula Vlll by reaction with lithium diorganocopper, e.g. lithium dimethylcopper, using the procedure of Posner and Whitten, Tetrahedron Letters, No. 53, 4647 1970).

The aldehydes of formula Vlll (R is hydrogen) can be prepared by the controlled oxidation of an allylic alcohol of formula [X (R is hydrogen) using chromic acid, manganese dioxide, and the like. The oxidation can be carried out using procedures described by Burrell et al, J. Chem. Soc. (C), 2,144 (1966); Weedon et al, J. Chem Soc. 2687 (1951) and Helv. Chim. Acta 32 1356 (1949). The allylic alcohols of formula [X are prepared by reduction of the corresponding ester or acid of formula A using lithium aluminum hydride or the like.

The allylic alcohols of formula lX, i.e. wherein R is hydrogen, are prepared by reduction of an ester or an acid of formula A. Ethers of formula 1X, i.e. wherein R' is not hydrogen. are prepared by etherification of an allylic alcohol of formula lX using conventional etherification methods such as by first converting the allylic alcohol into the corresponding halide of formula X in which X is bromo, chloro or iodo and then reacting the halide with the salt, e.g. the sodium or potas- XIII can be used as precursors for preparation of the sium salt, of an alcohol according the ether moiety deamines of the present invention as by treatment with sired. The allylic halides serve as precursors for the lithium aluminum hydride, and the like to the respecpreparation of the novel thiols and thioethers of fortive primary amine. mula XI. Thus, reaction of a halide of formula X with, 5 for example, thiourea or hydrogen sulfide provides the novel thiols. The thioethers can be prepared from the l l l l l l 4 I allylic halides by reaction with a mercaptide or by eth- R 'f z n 2' zhrf C erification of the thiol. SR- (XIII) R3 R14 R2 RISRIZRI 4 I I I I I 16 R C CII- (CH 'CII -CH- [CI-I C=-=E- C=ClI-CH -OR (IX) SR R3 R14 I," RZ "13 i1 I. l l 4 R -C--CII-(Cll Cll Cll (CH C C C-Cll Cll X ()t) R3 R14 R2 R13 R12 R1 4 1 l y l l 16 R -:I-CII- (Cll -CH -CII- (CH2 -C C C=ClI-CIl -SR (XI) sRlI In the above formulas R" is hydrogen, lower alkyl, In another embodiment of the present invention, cycloalkyl, aryl, aralkyl or carboxylic acyl. In formula there is provided novel amides of formula XIV R3 R14 R2 R13 R12 1 0 R8 4 I I ll R C CH- (CH2) H-CHZ-CH- (CH -C C C=CIl-C-N l SR R (XIV) IX, when R is hydrogen, then R is hydrogen. In forwhich can be prepared by reaction of an acid chloride mula XI, R" is lower alkyl, cycloalkyl, aralkyl or aryl. or acid bromide of formula A with an appropriate In another embodiment of the present invention, amine selected according to the amide moiety desired. there is provided novel amines of formula XII which The novel amides of the present invention can be preare prepared by reaction of an allylic halide of formula pared also by the reaction of a carbonyl of formula III X with an amine according to the amino moiety dewith a carbanion of the formula sired.

3 14 2 13 12 1 8 l I I l l l R4-C CH- (CH 'Cll *Cll- (CH -C L. C C=CIl-CH -N l SR v R (XII) wherein, R'O 0 R R 0 R each of R and R is hydrogen, alkyl, alkenyl, cycloal- \II I I l P- c-c=cu-c-ikyl, hydroxyalkyl, alkoxyalkyl, aryl or aralkyl, or when 6 taken together with the nitrogen atom to which they R'O R are attached, pyrrolidino, morpholino, piperazino or 4-alkylpiperazino.

which is generated by treatment of the corresponding;

In another embodiment of the present invention, phosphonamide with base such alkali metal hydride or there is provided nitriles of formula XIII which can be alkali metal alkoxide. The amides can be prepared also* prepared by reaction of a carbonyl of formula VI with by reaction of a carbonyl of formula VI with a carbana phosphonacetonitrile of the formula: ion or ylid of the following formulas, respectively;

in the presence of base such as an alkali metal hydride The novel compounds of formulas VII, VIII, IX, XI, or alkali metal alkoxide in an organic solvent such as Xll, XIII and XIV are useful for the control of insects tetrahydrofuran, benzene, dirnethylsulfoxide, toluene, in the same manner as the parent compounds of fordimethylformamide, ether, and the like. The nitriles of mula A. I the present invention can be prepared also by treat- The thioethers described herein are useful precursors ment of a primary amide of the present invention with i for preparing the respective sulfinyl and sulfonyl derivsodium borohydride using the procedure of Ellzey. Jr. atives by treatment of the thioether with sodium metaet al, U.S. Pat. No. 3,493,576. The nitriles of formula periodate, hydrogen peroxide, or the like, at a temperatives are useful for the control of insects in the same manner as the thioethers of formula A.

The compounds of formula I and the acetals and ketals of can be prepared from a compound of formula I, the preparation of which is described in application Ser. No. 187,897, filed Oct. 8, 1971, the disclosure of which is incorporated by reference.

Reaction of an aldehyde of formula I with hydrogen chloride, acetyl chloride or hydrogen bromide in a lower monohydric alcohol solvent medium provides acetals of formula I. Ketals of formula I can be prepared by ketalization of a ketone of formula I using a lower alkylene glycol such as ethyleneglycol in the presence of an acid catalyst followed by chlorination or bromination. Suitable procedures applicable to the preparation of halides of formula I and acetals and ketals thereof are described in U.S. Pat. Nos. 2,902,510, 3,381,039, 3,428,694 and 3,584,010.

The term cycloalkyl, as used herein, refers to a cyclic alkyl group of four to eight carbon atoms. The term aralkyl" refers to a monovalent hydrocarbon group in which an aryl group is substituted for a hydrogen atom of an alkyl group, such as benzyl, xylyl, mesityl, phenylethyl, methylbenzyl, naphthylmethyl and naphthylethyl containing up to twelve carbon atoms. The term aryl, as used herein, refers to an aromatic group of up to twelve carbon atoms. Typical aromatic groups include .phenyl, naphthyl, lower alkylphenyl such as methylphenyl, ethylphenyl, t-butylphenyl and isopropylphenyl, lower alkylthiophenyl such as methylthiophenyl, ethylthiophenyl and isopropylthiophenyl, lower alkoxyphenyl such as methoxyphenyl and ethoxyphenyl, halophenyl such as chlorophenyl, bromophenyl, iodophenyl and fluorophenyl, nitrophenyl, methylenedioxy phenyl, lower alkenylphenyl such as vinylphenyl and allylphenyl, phenylketones such as acetophenone, benzoic esters such as lower alkyl benzoate and benzamides such N-lower alkyl benzamide and N,N-di(lower alkyl) benzamide. In the case of substituted phenyl, the

substituent such as lower alkyl, lower alkylthio, lower alkoxy, halo, nitro, lower alkenyl, carbonyl, lower alkoxycarbonyl, cyano, and amido can be in one or more positions of the phenyl ring, usually in the para position. The term heterocyclic, as used herein, refers to a heterocyclic group consisting of four or five carbon atoms and one heteroatom which is oxygen, nitrogen or sulfur such as the heterocyclics pyridine, pyran, thiophan, pyrole, furan and thiophen.

The term hydroxyalkyl, as used herein, refers to an alkyl group substituted with one hydroxy group, e.g. hydroxymethyl, p-hydroxyethyl and 4-hydroxypentyl. The term alkoxyalkyl, as used herein, refers to an alkyl group substituted with one alkoxy group, e.g. methoxymethyl, Z-methoxyethyl, 4-ethoxybutyl, npropoxyethyl and t-butoxyethyl. The term alkenyl,

as used herein, refers to an ethylenically unsaturated hydrocarbon group, branched or straight chain, having a chain length of two to twelve carbon atoms, e.g., allyl, vinyl, 3-butenyl, 2-hexenyl and i-propenyl. Whenever any of the foregoing terms are modified by the word lower, the chain length of the group is not more than six carbon atoms with the exception of lower alkoxyalkyl and lower alkylthiaalkyl in which even a total chain length of twelve carbon atoms is the maximum. The term halogen substituted lower alkyl, as used herein refers to a lower alkyl group substituted with one to three halogen atoms such as chloromethyl, fluoromethyl, 2,2,2-trifluoro-2,2,2-trichloroethyl and the like.

The term carboxylic acyl, as used herein, refers to the acyl group of a carboxylic acid, anhydride or halide. The acyl group is determined by the particular carboxylic acid halide or carboxylic acid anhydride employed in the esterification. Although no upper limitation need be placed on the number of carbon atoms contained in the acyl group within the scope of the present invention, generally it contains from one to eighteen carbon atoms. Typical esters of the present invention include formate, acetate, propionate, enanthate, benzoate, trimethylacetate, trichloroacetate, trifluoroacetate, t-butylacetate, phenoxyacetate, cyclopentylpropionate, aminoacetate, B-chloropropionate, adamantoate, octadec-9-enoate, dichloroacetate, butyrate, pentanoate, hexanoate, phenylacetate, pmethylbenzoate, B-phenylpropionate, 3,4-dimethylbenzoate, p-isopropylbenzoate, cyclohexylacetate, stearate, methylacrylate, p-chloromethylbenzoate, pmethoxybenzoate and p-nitrobenzoate.

The term metal as used herein, refers to lithium, sodium, potassium, calcium, strontium, copper, manganese and zinc. The term alkyl" refers to a branched or straight chain, saturated aliphatic hydrocarbon of one to twelve carbon atoms. The term lower alkyl refers to an alkyl group having a chain length of one to six carbon atoms.

In addition to the compounds of the present invention having activity useful for the control of insects, the compounds have numerous other useful applications. For example, the esters of formula A of the present invention are useful lubricants and plasticizers for polymers such as SRB, polybutadiene, ethylene-propylene copolymers and polypropylene and aid in the processing and application of polymers. The aldehydes and ketones of formulas ll, lll, VI and Vlll are useful in perfumery compositions in view of their odorimparting properties. Thiolesters of formula Vll possess excellent lubricating properties per se and are useful also as lubricant additives. The amides of formula XIV are useful as anti-static agents for synthetic and naturala fibers. The amides can be incorporated into the fiber material by blending prior to extrusion or by application to the fiber after extrusion. The amines of formula Xll are useful wetting and cleansing agents per se for textiles and as intermediates therefor using the method of U.S. Pat. No. 2,169,976.

The presence of an olefinic bond at position C-2 and C-4 of the compounds of the present invention give rise to four isomers, each of which is embraced by the present invention. As mentioned above, a mixture of isomers is suitably employed for the control of insects such as a mixture containing the trans (2), trans (4) isomer and the cis (2), trans (4) isomer. The conditions of the syntheses described herein and the reactants can be selected so as to favor formation of one isomer such as the all trans isomer over the formation of other isomers. The selection of appropriate conditions and reactants to favor formation of one isomer over another will be apparent to those of ordinary skill in the art giving due consideration to the specific examples hereinafter. See also Pattenden and Weedon, supra and Corey et al, supra. In the specific examples hereinafter, when isomerism is not specified, it is understood to include a mixture of isomers which, if desired, can be separated using known separation methods. Hereafter, when only one designation of configuration is given, the designation refers to position C-2,3 and the configuration is taken to be trans at position C-4,5 when not otherwise specified.

The following examples are provided to illustrate the practice of the present invention. Temperature is given in degrees Centigrade.

EXAMPLE 1 Into a mixture of l() g. of 3,7-dimethyloct-6-en-l-al and 100 ml. of dry methanol is introduced 1.! equivalent of dry hydrogen chloride with cooling in ice-water. The mixture is then allowed to stand for about 24 hours at room temperature with stirring. Solvent is evaporated and residue taken up in other which is washed with water, dried and evaporated under reduced pressure to give l,l-dimethoxy-7-chloro-3,7- dimethyloctane.

The aldehydes under col. I are hydrochlorinated to give the respective compound under col. ll.

3 ,7-dimethylnon-6-en-l -al 3-methyl-7-ethylnon-6-en- 1 -al 3-ethyl7-m ethylnon--en- 1 -al 3 ,6,7-trimethyloct-6-en- 1 -al 3,6-dimethylhept-5-en-l -al 3 ,5,6-trimethylhept-5-en- 1 -al 2,5-dimethylhex-4-en- 1 -al 2,4,5-trimethylhex-4-en- 1 -al l,l-dimethoxy-7-chloro-3,7-dimethylnonane 1,l-dimethoxy-7-chloro-3-methyl-7-ethylnonane l, l -dimethoxy-7-chloro-3-ethyl-7-methylnonane l, l -dimethoxy-7-chloro-3,6,7-trimethyloctane 1,l-dimethoxy-6-chloro-3,6-dimethylheptane l,l-dimethoxy-6-chloro-3,5 ,6-trimethylheptane l, l -dimethoxy-5-chloro-2,5-dimethylhexane l, l -dimethoxy-S-chloro-2,4,5-trimethylhexane As an alternative method of preparation, there can be used the following procedure.

To 1.1 equivalents of acetyl chloride and 100 ml. of methanol, at about 10, is added l g. of 3,7-dimethyloct-o-en-l-al. The reaction is allowed to stand for about 24 hours at -l0 and then allowed to rise to room temperature. After one hour, solvent is removed by evaporation and the concentrate taken up in ether, washed with water and brine, dried over magnesium sulfate and evaporated to yield l,l-dimethoxy-7- chloro-3,7-dimethyloctane.

EXAMPLE 2 A mixture of 10 g. of l,l-dimethoxy-7-chloro-3,7- dimethyloctane, one equivalent of thiourea and I00 ml.

ill

of ethanol is refluxed for about 24 hours. Then a solution of 1.5 equivalents of sodium hydroxide in 50 ml. of water is added and the mixture refluxed for about two hours. After cooling to about room tempera ture, the solution is carefully acidified and ether is added. The organic layer is separated, washed with water, dried over calcium sulfate and evaporated to give 1,] -dimethoxy-7-mercapto-3,7-climethyloctane which is purified by distillation.

EXAMPLE 3 To a mixture of ml. of triethylene glycol and 42 g. of thiourea, at 75-80, is slowly added one equivalent of l,l-dimethoxy-7-chloro-3,7-dimethyloctane,

with stirring, keeping the temperature below When the reaction mixture is homogenous, the reaction is continued 12 hours and then one equivalent of tetraethylenepentamine is added slowly. Then the reaction mixture is heated to reflux until the head temperature is constant. The mixture is then distilled to give crude l, l -dimethoxy-7-mercapto-3,7-dimethyloctane which is purified by fractional distillation.

EXAMPLE 4 A solution of 10 g. of l,l-dimethoxy-7-chloro-3,7-

dimethyloctane, l,l equivalents of sodium hydrosulfide and 100 ml. of methanol is refluxed for 24 hours. After cooling, solvent is evaporated under reduced pressure and the concentrate taken up in either. The ether solution is washed with water, dried over magnesium sulfate and then evaporated to give l,l-dimethoxy-7- mercapto-3,7-dimethyloctane.

EXAMPLE 5 To 5 g. of magnesium covered with dry ether is added a crystal of iodine and then about 10 ml. of a solution of one equivalent of l,l-dimethoxy-7-chloro-3,7- dimethyloctane in 200 ml. of ether is added. The mixture is stirred until reaction begins and then remainder of solution is added slowly while heating to reflux. After addition is complete, reflux is continued for 1 hour. After cooling to 25-30, solid sulfur (one equivalent) is added portionwise while keeping the temperature about 30-35. After addition of the sulfur is com plete, the mixture is stirred for about 1 hour and then cooled to O-5 and about 200 ml. of aqueous ammonium chloride added slowly while maintaining low temperature. The organic phase is then separated and extracted with 2N sodium hydroxide. The basic extractis cooled in ice, acidified carefully by addition of cold aqueous EC] and extracted with ether. The ether extract is washed with saturated sodium chloride, dried over magnesium sulfate and evaporated to yield l,ldimethoxy-7-mercapto-3,7-dimethyloctane which is purified by distillation.

By use of the above procedure or, alternatively the procedure of Example 2, 3 or 4, each ofthe hydrochlorides under col. ll is converted into the respective mercaptan under col. lll.

ill

I l dimethoxy-7-mercapto-3,7-dimethylnonane l.l-dimcthoxy-7-mercapto-3-methyl-7-ethylnonane l,l-dimethoxy-7-mercapto-3et'hyl-7-methylnonane l,l-dimethoxy-7-mercapto-3,6,7-trimethyloctane l,l-dimethoxy-6-mercapto-3 ,6-dimethylheptane 1 1 1, l -dim ethoxy-6-mercapto-3 ,5,6-trimethylheptane l, l -dim ethoxy-S-mercapto-2,5-dimethylhexane l ,1-dimethoxy--mercapto-2,4,5-trimethylhexane EXAMPLE 6 To a mixture of g. of 1,1-dimethoxy-7-mercapto- 3,7-dimethyloetane, one equiv. of sodium methoxide and 100 ml. of methanol is added 1.5 equivalents of methyl iodide. The mixture is stirred for 2 hours at room temperature and then refluxed for 2 hours. After cooling to room temperature, solvent is removed by evaporation and the residue taken up in ether. The ether solution is washed with water, dried and evaporated under reduced pressure to give l,I-dimethoxy-7- methylthio-3,7-dimethyloctane which can be purified by chromatography or distillation.

A mixture of 5 g. of l,l-dimethoxy-7-methylthio-3,7- dimethyloctane, 50 ml. of aqueous tetrahydrofuran (1:1) and 10 ml. of 3N hydrochloric acid is stirred at room temperature until hydrolysis is completed as followed by thin layer chromatography to give crude 7- methylthio-3,7-dimethyloctane-l-al which is worked up by extraction with ether and purified by chromatography.

Following the procedure of this example, there is prepared the methylthio compounds under col. IV from the respective mercaptan under col. III.

7-methylthio-3 ,7-dimethylnonan- 1 -al 7-methylthio-3-methyl-7-ethylnonan- 1 -al 7-methylthio-3-ethyl-7-methylnonan- 1 -al 7-methylthio-3,6,7-trimethyloctanl -al 6-methylthio-3 ,-dimethylheptanl -al 6-methylthio-3,5,6-trimethylheptan- 1 -al 5-methylthio-2,5-dimethylhexan-l-al 5-methylthio-2,4,S-dimethylhexan-l-al EXAMPLE 7 Sodium methoxide (1.2 g. of sodium and 30 ml. of methanol) is added slowly to a mixture of 6.4 g. of 7- methylthio-3,7-dimethyloctan-l-al and 10 g. of diethyl 3-methoxycarbonyl-2-methylprop-2-enyl phosphonate (about 77% trans) in 50 ml. of dimethylformamide, under nitrogen and at about 0, with stirring. After addition is complete, the reaction is left three hours at room temperature and worked up by extraction with hexane/ether to yield cis/trans methyl ll-methylthio- 3,7,1l-trimethyldodeca-2,4-dienoate mostly the trans, trans isomer.

By repeating the above process, using each of the aldehydes under col. IV as the starting material, there is prepared the respective methyl ester under col. V.

methyl 1 l-methylthio-3,7,l l-trimethyltrideca-2,4-

dienoate methyl 1 l-methylthio-3,7-dimethyl-l l-ethyltrideca- 2,4-dienoate methyl 1 l-methylthio-3,l l-dimethyl-7-ethyltrideca- 2,4-dien0ate methyl 1 l-methylthio-3,7,l0,l l-tetramethyldodeca- 2,4'dienoate methyl l0-methylthio-3 ,7, l O-trimethylundeca-2,4-

dienoate methyl l0-methylthio-3 ,7,9, l O-tetramethylundeca- 2,4-dienoate 12 methyl 9-methylthio-3 ,6,9-trimethyldeca-2,4-

dienoate methyl 9-methylthio-3 ,6,8,9-tetram ethyldeca-2,4-

dienoate EXAMPLE 8 To 350 ml. of ethanol, 105 ml. of water and ml. of 50% aqueous sodium hydroxide is added 46.5 g. of methyl 1 l-methylthio-3,7,l l-trimethyldodeca-2,4- dienoate. The mixture is refluxed for about 18 hours. After cooling. alcohol is removed in vacuo. Water is added followed by acidification and then extraction with ether to yield l l-methylthio-3,7,l l-trimethyldodeca-2,4-dienoic acid.

By use of the above process, the other esters under col. V are hydrolyzed to the respective free acid.

EXAMPLE 9 EXAMPLE l0 To 0.6 g. of ll-methylthio-3,7,l l-trimethyldodeca- 2.4-dienoic acid in IQ ml. of dry benzene is added 0.23 ml. of oxalyl chloride at room temperature. After about 2 hours, there is added 0.25 ml. of S-thiabutanl -ol and the reaction allowed to stand for about 2 hours. The reaction is worked up as in Example 9 to yield 3'- thiabutanyl l l-methylthio-3,7,l l-trimethyldodeca-2,4- dienoate.

EXAMPLE 1 1 Sodium ethoxide (9 g. sodium in 600 ml. of ethanol) is added slowly to a mixture of 54.5 g. of 7-methylthio- 3,7-dimethyloctan-l-al and g. of diethyl 3- ethoxycarbonyl-2-methylprop-2-enyl phosphonate (about 49% trans) in one liter of dimethylformamide, under nitrogen and at 0, with stirring. The mixture is allowed to stand overnight at about 5 and the reaction worked up by extraction with ether, washing with water and brine and filtering through Florisil to yield ethyl ll-methylthio-3,7,l l-trimethyldodeca-2,4-dienoate as a cis/trans mixture, mostly trans, trans.

EXAMPLE l2 To a solution of0.5 g. of l l-methylthio-3,7,l l-trimethyldodeca-2,4-dienoic acid in 15 ml. of benzene is added, with stirring, an equivalent amount of potassium hydride. The mixture is stirred at room temperature for about 2 hours and then evaporated to give potassium l l-methylthio-3,7,l l-trimethyldodeca-2,4-dienoate.

In place of KH, there can be used KOH, NaOH, and the like to form the corresponding salt.

EXAMPLE 13 To a solution of 2 g. of methyl ll-methylthio-3,7,l ltrimethyldodeca-2,4,IO-trienoate and 20 ml. of dry ether, at 78 is added slowly about 0.4 g. of lithium aluminum hydride in dry ether. The mixture is allowed to stand about 1 hour after addition is complete and then allowed to warm up to room temperrature. Then 2.5 ml. of acetic acid is added. The mixture is then washed with ice water and the organic phase separated which is dried over magnesium sulfate and evaporated to yield l1-methylthio-3,7,1 l-trimethyldodeca-2,4- dien-l -ol.

EXAMPLE 14 A mixture of 0.18 g. of NaH (rinsed with hexane), 5 ml. of tetrahydrofuran and 0.8 g. of diethyl diethylaminocarbonylmethyl phosphonate, under nitrogen, is stirred 0.5 hours at 0. To the mixture is slowly added 1.0 g. of -methylthio-6,10-dimethy1undec-3- en2-one. After addition is complete, the reaction is left at room temperature for about 30 minutes and then chromatographed on silica with ether to yield N,N- diethyl 1 l-methylthio-3,7,1 1-trimethyldodeca-2,4- dienamide (mostly trans-2-trans-4), which can be further purified by chromatography.

EXAMPLE To sodium hydride (0.7 g.), previously washed with hexane, under nitrogen, is added 75 ml. of dry tetrahydrofuran and then, after cooling to 0, 5.1 g. of diethyl phosphonoacetonitrile is added slowly. The mixture is stirred for about 30 minutes and then added slowly to 6.8 g. of l0-methylthio-6,lO-dimethylundeca-3-en- 2-0ne at room temperature with stirring. The mixture is stirred for about 12 hours and then poured into saturated sodium chloride at 0. The layers are separated and the organic layer dried over magnesium sulfate and evaporated to yield 1 1-methylthio-3,7,l 1-trimethyldodeca-2,4-dienenitrile.

EXAMPLE 16 To a stirred solution of 2.5 g. of l l-methylthio- 3,7,1l-trimethyldodeca-2,4-dienoic acid in 20 ml. of dry-ether is added slowly at 0, 23 m1. of a one molar solution of ethyl lithium in benzene. After about three hours at 20, the mixture is poured into iced 1N hydrochloric acid 100 ml.) with vigorous stirring. The ether layei is separated, combined with ethereal washings of the aqueous phase, washed with water, saturated potassium bicarbonate and then saturated brine, dried over magnesium sulfate and concentrated under reduced pressure to yield 13-methylthio-5,9,1B-trimethyltetradeca-4,6-dien-3-one, which can be purified by chromatography.

By using methyl lithium, cyclopentyl lithium and phenyl lithium in the above process in place of ethyl lithium, there is prepared 12-methylthio-4,8,12'trimethyltrideca3,5-dien-2-one, cyclopentyl 10-methylthio- 2,6,10-trimethylundeca-1,3-dienyl ketone and phenyl 10-methylthio-2,6,IO-trimethylundeca-l,3-dieny1 ketone, respectively.

EXAMPLE 17 Sodium ethoxide (prepared from 0.2 g'. of sodium and 12 ml. of ethanol) is slowly added to a mixture of 1.1 g. of 7-methylthio-3,7-dimethyloctan-1-al, diethyl 3-ethoxycarbonyl-2-methy1-prop-2-eny1-phosphonate (1.6 g.) and 50 ml. of dimethylformamide, with stirring, under nitrogen, at 0. The reaction is stirred for 1.5 hours after addition is complete and then worked up by extraction with ether to yield ethyl ll methylthio- 3.7.1 1-trimethyldodeca-Z,4-dienoate.

EXAMPLE 18 To a mixture of 10 g. of 7-methylthio-3,7-

dimethyloctan-l-al, 17 g. of diethyl 3-ethoxycarbonyl- Z-methylprop-Z-enyl phosphonate (77% trans), and ml. of dimethylformamide, under nitrogen, 0", with stirring, is added sodium isopropanolate (prepared from 1.5 g. of sodium in 150 ml. of isopropanol). After addition is complete, the reaction is stirred for 18 hours at room temperature and then worked up by extraction with hexane to yield isopropyl 11-methy1thio-3.7,11- trimethyldodeca-2,4-dienoate (mostly trans-2,trans-4) which can be chromatographed and distilled for further purification.

EXAMPLE 19 A mixture of 5 g. of 7-mercapto-3,7-dimethyloctan- 1-al 8.5 g. of di-isopropyl 3-ethoxycarbony1-2- methylprop-2'enylphosphonate, and 40 ml. of dimethylformamide, under nitrogen and cooled in an ice-bath, is stirred for 0.5 hcfir? and then ground NaOH (1.165g.) is added. The reaction mixture is stirred at room temperature for 3 hours and then hexane/water (1/1) added. The organic layer is washed with water and brine, dried over calcium sulfate and concentrated. The concentrate is filtered through Florisil using hexane and hexane/ether. The filtrate is concentrated and then distilled to yield ethyl 1 l-mercapto-3,7,1 1- trimethyldodeca-2,4-dienoate (mostly trans-2, trans- 4).

The process of this example is repeated with the exception of using di-isopropyl 3-isopropoxy carbony1 2- methylprop-Z-enylphosphonate to prepare isopropyl 1 1-mercapto-3,7,1 1-trimethyldodeca-2,4-dienoate.

EXAMPLE 20 To 0.55 g. of 1 l-methylthio-3,7,l l-trimethyldodeca- 2,4-dienoic acid in 10 ml. of dry benzene is added 0.21 ml. of oxalyl chloride. The mixture is stirred occasionally at room temperature for about 2.5 hours. The mixture is cooled in cold water and then 0.18 ml. of ethylmercaptan is added with stirring. The mixture is then stirred at room temperature for about 24 hours. Ether and saturated sodium bicarbonate is added and the organic phase separated. The organic phase is washed with aqueous sodium bicarbonate, saturated sodium chloride, dried over calcium sulfate and evaporated to yield ethyl 1 1-methylthio-3,7,l l-trimethyl-thioldodeca-2,4-dienoate.

Thiol esters are prepared using each of n-propyl mercaptan ispropyl mercaptan, isobutyl mercaptan, s-butyl mercaptan, n-butyl mercaptan, benzyl mercaptan, cyclopentyl mercaptan B-phenylethyl mercaptan, t-amyl mercaptan and n-hexyl mercaptan in reaction with 11 methy1thio-3,7,11-trimethy1dodeca-2,4-dienoyl chloride or the sodium salt of l 1-methy1thio-3,7,1l-trimethyldodeca-2,4-dienoic acid to yield n-propyl 1 1- methylthio-3,7,11-trimethyl-thioldodeca-2,4-dienoate, isopropyl 1 1-methylthio-3,7,1 l-trimethyl-thioldodeca- 2,4-dienoate, etc.

EXAMPLE 21 Sodium hydride (1.7 g., 57% in oil) is washed three times with dry hexane. The hexane is removed and 15 m1. of dry tetrahydrofuran is added. N,N-Diethyl diethoxyphosphonoacetamide (0.9 g.), dissolved in 5 m1. of dry tetrahydrofuran, is added and stirred for about 40 minutes (0). Then about 0.7 g. of 10- methylthio-6,10-dimethyldodec-Zl-en-Z-one in 5 ml. of

dry tetrahydrofuran is added with stirring and cooling with an ice-bath. The ice-bath is removed after addition is completed and stirring continued for about 2 hours. Then the mixture is poured into water and extracted with ether. The ether extracts are combined, washed with water, dried over magnesium sulfate and evaporated under reduced pressure to yield N,N-diethyl l lmethylthio-3,7,l l-trimethyltrideca-2,4-dienamide.

EXAMPLE 22 To 0.5 g. of the acid of Example 8 in 10 ml. of benzene, under nitrogen is added 0.17 ml. of oxalyl chloride which is stirred for about 45 minutes and then allowed to stand 2 hours. Two ml. of isopropanol is added. After 3 hours, ether is added and organic layer separated. The organic layer is washed with aqueous sodium bicarbonate and brine, dried over calcium sulfate and concentrated under reduced pressure to yield isopropyl l 1-methylthio-3,7,l l-trimethyldodeca-2,4- dienoate which can be purified by chromatography and distillation.

Using the foregoing procedure, each of 3- thiacyclohexanol, 2,2,2-trifluoroethanol, t-butanol, 2- methoxyethanol, 2-methylthiethanol and s-butanol provides 3'-thiacyclohexyl l l-methylthio-3,7,l ltrimethyldodeca-2.4-dienoate, 2',2,2'-trifluoroethyl l l-methylthio-3,7,l l-trimethyldodeca-2,4-dienoate, t-butyl l l-methylthio- 3 7] l-trimeth yldodeca 2,4- dienoate, 2-methoxyethyl l l-methylthio-3,7,l ltrimethyldodeca-2,4-dienoatc, 2methylthiaethyl l lmethylthio-3,7,ll-trimethyldodcca-2,4-dienoatc, and s-butyl l l-methylthio-3,7,l l-trimethyldodeca-2,4- dienoate.

EXAMPLE 23 To a mixture of 4 g. of ll-methylthio-3,7,l ltrimethyldodeca-2,4-dien-l-ol and 25 ml. of ether at is added a solution of 5 ml. of phosphorus tribromide in 18 ml. of benzene over about minutes. The reaction mixture is stirred at 0 for 2 hours. The mixture is then poured onto ice and extracted with pentane. The organic phase is washed with aqueous sodium bicarbonate, water and brine, dried over magnesium sulfate and evaporated to yield l1-methylthio-3,7,lltrimethyldodeca-2,4-dienyl bromide.

Phosphorus trichloride is reacted with llmethylthio-3,7,ll-trimethyldodeca-2,4-dien-l-ol following the above procedure to prepare 1 l-methylthio- 3,7,l l-trimethyldodeca-2,4-dienyl chloride.

EXAMPLE 24 EXAMPLE 25 To 126 mg. of a 57% dispersion of sodium hydride in oil is added pentane. The pentane is removed and the sodium hydroxide washed several times with pentane.

To the washed sodium hydride is added 582 mg. of diethyl acetyl-methylphosphonate in 5 ml. of tetrahydrofuran at l0 under argon. After several minutes, the solution is transfered to a solution of 425 mg. of 7- methylthio-3,7-dimethyloctan- 1 -al in about 4 ml. of dry tetrahydrofuran under argon over a period of about 20 minutes at room temperature. After about 2 hours, water is added followed by addition of ether and the layers separated. The organic layer is washed with saturated sodium chloride, dried over sodium sulfate and evaporated under reduced pressure to yield 10- methylthio-6,lO-dimethylundec-3-en-2-one.

EXAMPLE 26 One grams of triphenylphineacetylmethylene and 425 mg. of 7-methylthio-3,7-dimethylnonan-l-al are dissolved in 10 ml. of toluene and refluxed under nitrogen overnight. The toluene is distilled off and the formed triphenylphosphine oxide crystallized by addition of pentane. Filtration and evaporation of the pentane gives a residue, which is further purified by perparative thin layer chromatography to yield 10- methylthio-6,lO-dimethyldodec3-en-2-one.

EXAMPLE 27 41 Grams of 7-methylthio-3,7-dimethyloctan-1-al and g. of recrystallized (ethyl acetate0 triphenylphosphineacetylmethylene [Ramirez et al., J. Org. Chem. 22, 4] (I957) are refluxed in one liter of dry toluene for IS hours, under nitrogen. Most of the solvent is removed in vacuo, 500 ml. pentane is added and the mixture filtered. The flask and the triphenylphosphine oxide filter cake are washed several times with pentane. The filtrate is concentrated under vacuum to yield lO-methylthio-6, l O-dimethylundec-3-en-2-one.

EXAMPLE 28 The carbanion of diethyl carbomethoxymethyl phosphonate is reacted with l0-methylthio-6,l0- dimethylu ndec-3-en-2-one and l 0-methylthio-6, l 0- dimethyldodec-3-en-2-one to prepare methyl 1 l-methylthio-3,7,l l-trimethyldodeca-2,4-

dienoate and methyl ll-methylthio-3,7,l1- trimethyltrideca-2,4-dienoate.

EXAMPLE 29 One gram of ethyl l l-mercapto-3,7,l l-trimethyldodeca-2,4-dienoate in 10 ml. of diglyme is added dropwise to a slurry of l g. of sodium hydride in 10 ml. of diglyme under nitrogen. To this mixture is added 0.9 g. of cyclohcxylchloride. The reaction mixture is stirred at about 25 for 30 minutes and then quenched in ice water. The organic phase is separated and aqueous phase reextracted with ether. The organic materials are washed with water, dried over sodium sulfate and evaporated to yield ethyl l l-cyclohexylthio-Zl,7,l ltrimethyldodeca 2,4-dienoate.

By using each of benzyl chloride and cyclopentyl chloride in the foregoing procedure, the corresponding benzyl thioether and cyclopentyl thioether is prepared.

EXAMPLE 30 A mixture of 9.0 g. of 7-methylthio-3,7- dimethyloctan-l-al and 15 g. of triphenylphosphineacetylmethylene in ml. of dry toluene, under nitrogen, is refluxed for 20 hours. Thereafter, the toluene is evaporated and pentane added to remove tri- 17 phenylphosphine. After concentration, the product is distilled to yield l-methylthio6,l0-dimethylundec-3- en-Z-one. The thus-prepared ketone is reacted with the carbanion of diethyl carbethoxymethylphosphonate to prepare ethyl l l-methylthio-3,7,l l-trimethyldodeca2,4-dienoate.

EXAMPLE 3] Two grams of l l-methylthio-3,7,l l-trimethyltrideca- 2,4-dienoic acid chloride is added to 50 ml. of benzene, cooled to 0 and saturated with ammonia under nitrogen. The mixture is allowed to stand for about one hour and then it is washed with water, dried over sodium sulfate and evaporated to yield 1 l-methylthio-3,7,l ltrimethyltrideca-2,4-dienamide.

EXAMPLE 32 Three grams of l l-methylthio-3,7,l l-trimethyldodeca-2,4-dienoyl chloride in benzene is mixed with 2.5 g. of diethylamine in benzene and the resulting mixture allowed to stand at room temperature for about 2 hours. The mixture is concentrated under reduced pressure and the residue taken up in benzene, washed with dilute aqueous sodium bicarbonate and water, dried over sodium sulfate and evaporated to yield N,N- diethyl l l-methylthio-3,7,l l-trimethyldodeca-2,4- dienamide.

By use of the foregoing procedure, each of dimethylamine, ethylamine, pyrrolidine, piperidine, aniline, morpholine and 2-methoxyethylamine is reacted with the acid chloride to yield the corresponding amide, that is, N,N-dimethyl l l-methylthio-3,7,l l-trimethyldodeca-2,4-dienamide, N-ethyl l l-methylthio-3,7,l ltrimethyldodeca-2,4-dienamide, etc.

EXAMPLE 33 Ten grams of l-bromo l l-methylthio-3,7,l ltrimethyldodeca2,4-diene is mixed with 50 ml. of benzene, cooled to -10 and saturated with ammonia. The resulting mixture is stirred for 4 hours allowing the temperature to rise to about while maintaining dry conditions. The mixture is washed with dilute sodium hydroxide and then evaporated under reduced pressure to yield ll-methylthio-3,7,ll-trimethyldodeca-2,4- dienylamine.

EXAMPLE 34 Five grams of ll-methylthio-3,7,ll-trimethyldodeca2,4-dienylbromide in ml. of benzene is mixed with 4 g. of diethylamine and the mixture stirred for about three hours. Methylene chloride (50 ml.) is added and the mixture washed with dilute sodium hydroxide and then water and evaporated to yield N,N- diethyl l l-methylthio-3 ,7,l l-trimethyldodeca-2,4- dienylamine.

Other amines of the present invention are prepared by use of the foregoing procedure using an amine of the formula:

such as dimethylamine, ethylamine, methylamine, pyrrolidine, morpholine, 4-ethylpiperazine, and the like, in place of diethylamine. Thus, there is prepared N,N- dimethyl l l-methylthio-3,7,l l-trimethyldodeca2,4-

18 dienylamine, N-ethyl ll-methylthio-3,7,l l-trimethyl dodeca-2,4-dienylamine, etc.

EXAMPLE 35 To one g. of ll-methylthio-3,7,l l-trimethyldodeca- 2,4-dien-l-ol in 20 ml. of dry ether is added one molar equivalent of diazoethane. One drop of borontrifluoride is added and after 1 hour at 0 the mixture is washed with water and organic phase evaporated to yield the ethyl ether of l l-methylthio3,7,l ltrimethyldodeca-2,4-dienl-ol.

The use of diazomethane in the foregoing procedure affords l-methoxy-l l-methylthio-3,7,l l-trimethyldodeca-2,4-diene.

EXAM PLE 36 One g. of 1 l-methylthio-3,7,l l--trimethyldodeca-2,4- dien-l-ol in l0 ml. of diglyme is added dropwise to a slurry of l g. of sodium hydride in 10 ml. of diglyme under nitrogen. To this mixture is added 0.9 g. of cyclohexylchloride. The reaction mixture is stirred at about 25 for 30 minutes and then quenched in ice water, dried overe sodium sulfate and evaporated to yield the cyclohexyl ether of 'll-methylthio-3,7,lltrimethyldodeca2,4-dien-1-ol.

EXAMPLE 37 To a suspension of l g. of sodium hydride in 10 ml. of tetrahydrofuran, under argon, and cooled to 4, is slowly added 4 g. of p-ethylphenol in 15 ml. of tetrahydrofuran. The mixture is stirred for about 8 hours. To the mixture, cooled in an ice-bath, is slowly added 4 g. of l l-methylthio-3,7,l l-trimethyldodeca-2,4-dienyl bromide in ether. After about two hours, the mixture is warmed to room temperature, 25 ml. of hexamethylphosphoramide is added and the mixture heated at for about 48 hours. The mixture is then poured into water and extracted with ether. The ethereal extracts are combined, washed with dilute aqueous sodium hydroxide, water and brine, dried over sodium sulfate and then evaporated to yield ll-methylthio-3,7,l l-trimethyldodeca2,4-dienyl p-ethylphenyl ether.

EXAMPLE 38 A. To 210 ml. ofa 0.5M solution of sodium metaperiodate (aqueous methanol 1:1 at 0 is added 0.l mole of methyl 1 l-methylthio-3,7,l l-trimethyldodeca-2,4- dienoate. The mixture is stirred at 0 for about 4 hours and then filtered. The filtrate is diluted with water and then extracted with chloroform. The extract is dried over magnesium sulfate and solvent removed by evaporation to yield methyl 1 l-methylsulfinyl-3,7,l ltrimethyldodeca-2,4-dienoate which can be purified by chromatography.

B. To 200 ml. of aqueous methanol (121) containing 0.2 mole of sodium metaperiodate is added 0.1 mole of methyl 1 l-methylthio-Ii,7,l l-trimethyldodeca-2,4- dienoate The mixture is maintained at about 30 for 6 hours. After cooling, the mixture is filtered to remove precipitated sodium iodate. The filtrate is diluted with water and then extracted with chloroform. The extract is dried over magnesium sulfate and solvent removed by evaporation to yield methyl 1 l-methylsulfonyl- 3,7,1 l-trimethyldodeca-2,4-dienoate, which can be purified by chromatography.

One g. of l l-methylthio-3,7,l l-trimethyldodeca-2,4-

dien-l-ol in 10 ml. of dry pyridine is cooled to 1 and 2 ml. of acetic anhydride is added dropwise. The reac tion is left about four hours at -l0. Then, ice water (about 5 ml.) is added dropwise. After about 0.5 hour,

excess water is added and the mixture extracted with ether. The ethereal phase is washed with water, dried over calcium sulfate and solvent removed to yield 1- acetoxy-l l-methylthio3,7,l l-trimethyldodeca-2,4- diene.

By using other carboxylic anhydrides in the process of this example in place of acetic anhydride, the respective C-l esters are prepared.

EXAMPLE 40 EXAMPLE 4! To a suspension of 30 g. of 3-formyl-2-methylprop-2- enyltriphenylphosphonium chloride in 200 ml. of absolute ether, under nitrogen, at room temperature, is added a solution of 1.1 equivalents of phenyl lithium in ether. After about 30 minutes, the mixture is cooled to 0 and one equivalent of 7-methylthio3,7- dimethyloctan-l-al in ether is added. The reaction is brought to room temperature and refluxed for l2 hours. The mixture is allowed to cool and then is tiltered and the filter cake washed with ether. The washings and filtrate are evaporated under reduced pressure and the concentrate fractionally distilled to give 11- methylthio-3,7,l l-trimethyldodeca-2,4-dien-l-al which is further purified by chromatography.

EXAMPLE 42 A. Anhydrous methanol (60 ml.) is saturated with dry hydrogen chloride at 0. To the saturated solution i is added 7.8 g. of 3,7-dimethyloct-6-en-l-ol, with stirring, over a period of 5 minutes. After stirring for 15 20 minutes at 0, the ice bath is removed and nitrogen bubbled through the solution while it warms to room temperature. Solvent and residual hydrogen chloride are removed by evaporation under reduced pressure to give 7-chloro3,7-dimethyloctan-l-ol.

B. To an ice-cold solution of 19.0 g. of dry pyridine and 300 ml. of methylene chloride is added 12.0 g. of chromium trioxide under nitrogen. After stirring for 30 minutes. at 0, to the dark brown reaction mixture is added 3.9 g. of 7-chloro3,7-dimethyloctan-l-o. The ice bath is then removed and stirring continued for 15 minutes. The solution is then decanted away from the residue and filtered through a 5 cm. by 2 cm. column of Activity lV neutral alumina. Evaporation of the solvent yields 7-chloro-3,7-dimethyloctan-l-al, as a clear, colorless oil.

C. To a mixture of 30 mg. of ammonium chloride, l0 ml. of methanol and one ml. of trimethyl orthoformate is added 500 mg. of 7-chloro-3,7-dimethyloctan-l-al. The reaction mixture is stirred at room temperature overnight under nitrogen. The mixture is then neutralized with sodium methoxide and the methanol removed under reduced pressure. The residue is taken up in ether, washed with sodium bisulfite and then water, dried over calcium sulfate, and solvent removed under reduced pressure to yield the dimethylacetal 1,1- dimethoxy-7-chloro-3,7-dimethyloctane).

By following the procedure of this example, other dimethyl acetal precursors of formula I can be prepared using as the starting an alcohol of the formula (l"):

The alcohols of formula I" can be prepared by the reduction of a carbonyl of formula 1 such as the aldehydes thereof (R is hydrogen) by treatment with sodium borohydride or the like. A representative procedure for reduction of the carbonyls of formula I to the alcohols of formula ll" is as follows. To an ice-cooled solution of l.0 g. of 3,7-dimethyloct-6-en-l-al in 50 ml. of methanol and 3 ml. of water is added 1.0 g of sodium borohydride. The reaction mixture is stirred and then allowed to stand 3 hours at room temperature. Acetic acid (2 ml.) is added and the mixture concentrated under reduced pressure followed by dilution with water. The diluted concentrate is extracted with ethyl acetate and the extracts combined, washed with water, dried and evaporated to yield 3,7-dimethyloct-6-en-lol.

EXAMPLE 43 To a mixture of 20 ml. of benzene, one ml. of ethylene glycol and 10 mg. of p-toluenesulfonic acid is added 500 mg of 7-chloro-3,7-dimethyloctan-l-al. The mixture is refluxed for 16 hours and water is removed by means of a DeanStark trap. After cooling to room temperature, the mixture is poured into ether and washed with aqueous sodium bicarbonate and then water. After drying over calcium sulfate, solvent is removed under reduced pressure to yield the ethylene ketal (l,l-cycloethylenedioxy-7-chloro-3,7- dimethyloctane).

The procedure of this example can be used to prepare the other cycloethylene ketals of the carbonyls of formula I.

EXAMPLE 44 A mixture of 4 g. of citronellol (3,7-dimethyloct-6- en-l-ol), 0.490 g. of p-toluenesulfonic acid and 0.290 g. of hydroquinone is placed in a stainless steel screw cap bomb having an internal volume of 45 ml. The bomb is cooled in dry ice. Methyl mereaptan (9 g.) is. introduced directly into the bomb through the valve head. The bomb is sealed, left overnight at room temperature and then heated to 220 in an oil bath for about 72 hours. After cooling in dry ice, the bomb valve is opened and the reaction mixture is carefully poured into aqueous sodium hydroxide solution. Ether is added and the organic layer is separated,

washed with 5% NaOH, 5% HCl and water, dired over calcium sulfate and concentrated with vacuo to yield 7-methylthio-3,'7-dimethyloctanl -ol.

EXAMPLE 45 Twenty grams of citronellol, 2 g. of p-toluenesulfonic acid and 9 g. of methyl mercaptan are reacted as described in Example 44 except that a temperature of 140 is used instead of 220, to give 7-methylthio-3,7- dimethyloctan-l-ol.

EXAMPLE 46 To 2.04 g. (10 mmol.) of 7-methylthio-3,7- dimethyloctanl-ol in ml. of freshly distilled dimethylsulfoxide, under nitrogen at 20, is added via syringe 1 1.2 ml. (80 nfmol.) of triethylamine while stirring vigorously. Sulfur trioxide-Z pyridine complex (10.28 g.,

64 mmol.) in dimethylsulfoxide (50 ml.) is added slowly to the mixture via dropping funnel under the same conditions. After addition is complete, the reaction mixture is stirred for 5 minutes and poured into cold water. Hexane is added and the organic layer separated, washed well with water and dried over calcium sulfate. Evaporation of the solvent at reduced pressure affords 7-methylthio-3,7-dimethyloetan-l-al.

EXAMPLE 47 Sodium ethoxide (490 mg.) is added, during about 50 fate and evaporated to yield ethyl 7-methylthio-3,7,l 1-

trimethyldodeca-2,4-dienoate, predominantly the trans, trans isomer, which can be purified by chroma tography or distillation.

EXAMPLE 4% To 5 g. of citronellol in 30 ml. of glacial acetic acid, stirring under nitrogen, is added dropwise 1 L26 g. of a 30 .32% solution of hydrobromic acid in acetic acid and the mixture is stirred at room temperature for about 18 hours. The reaction mixture is then diluted with water and extracted with pentane. The organic phase is washed with water until neutral, dried over magnesium sulfate and the solvent removed at reduced pressure to give l-aeetoXy-7-bromo-3 ,7- dimethyloctane.

EXAMPLE 49 Three grams of 1-acetoxy-7-bromo-3 ,7-

dimethyloctane and 20 ml. of aqueous ethanol is stirred under nitrogen for about three hours. Thiourea (760 mg.) is added and the reaction mixture is refluxed under nitrogen for one hour. Then 500 mg. of sodium hydroxide in 18 ml. of water is added to the mixture and reflux is continued for 12 more hours. After cooling, the reaction mixture is poured into water and cxtraeted with pentane. The organic extracts are washed with water and brine, dried over magnesium sulfate and concentrated under vacuum to yield 7-mereapto3,7- dimethyloctan-l-ol, which can be purified by chromatography.

What is claimed is:

1. A compound selected from those of the following formula:

r i f? o R ll wherein,

each of m and n is 0 or the positive integer 1,, 2, or

R is hydrogen, lower alkyl,cycloa1kyl,aralkyl or aryl; each of R and R is lower alkyl; each of R', R, R and R" is hydrogen or lower alkyl; R is alkyl; and each of R and R is hydrogen, alkyl, alkenyl, or cycloalkyl. 2. A compound according to claim 1 wherein m is l; n is O or 1; R is hydrogen, methyl or ethyl; each of R and R is hydrogen; each of R, R and R is methyl; and R is methyl or ethyl.

3. A compound according to claim 2 wherein R is hydrogen and n is l.

4. A compound according to claim 3 wherein each of- 5 R and R is hydrogen, methyl or ethyl and R is methyl or ethyl.

5. The compound, N,N-diethyl ll-methylthio- 3,7,1l-trimethyldodeca-2,4-dienamide, according to claim 4.

6. The compound N,N-diethyl l l-mcthylthio-3,7,l l-

trimethyltrideca-2,4-dienamide, according to claim 5. =l t 

1. A COMPOUND SELECTED FROM THOSE OF THE FOLLOWING FORMULA:
 2. A compound according to claim 1 wherein m is 1; n is 0 or 1; R is hydrogen, methyl or ethyl; each of R12 and R13 is hydrogen; each of R1, R2 and R3 is methyl; and R4 is methyl or ethyl.
 3. A compound according to claim 2 wherein R14 is hydrogen and n is
 1. 4. A compound according to claim 3 wherein each of R8 and R9 is hydrogen, methyl or ethyl and R is methyl or ethyl.
 5. The compound, N,N-diethyl 11-methylthio-3,7,11-trimethyldodeca-2,4-dienamide, according to claim
 4. 6. The compound N,N-diethyl 11-methylthio-3,7,11-trimethyltrideca-2,4-dienamide, according to claim
 5. 